PROTEOLYTIC INACTIVATION OF MAP-KINASE-KINASE BY ANTHRAX LETHAL FACTOR

Anthrax lethal toxin, produced by the bacterium Bacillus anthracis, is the major cause of death in animals infected with anthrax. One compon ent of this toxin, lethal factor (LF), is suspected to be a metallopro tease, but no physiological substrates have been identified. Here it i s shown that LF is a protease that cleaves the amino terminus of mitog en-activated protein kinase kinases 1 and 2 (MAPKK1 and MAPKK2) and th at this cleavage inactivates MAPKK1 and inhibits the MAPK signal trans duction pathway. The identification of a cleavage site for LF may faci litate the development of LF inhibitors.